The long-term objective is to clarify at the chemical level the fate of selenium in living organisms. This information is needed to better understand its functions as an essential trace element, its anticarcinogenic action, and toxic effects of excess selenium. There is great interest in supplementing the human diet with selenium to correct nutritional deficiencies or improve oxidant defense mechanisms, and recent human cancer chemoprevention trials also have used selenium supplementation. There is rather limited knowledge about forms of selenium in tissues, and the mechanisms by which inorganic forms of selenium such as sodium selenite or selenate are firmly and selectively incorporated into proteins. There is evidence that selenoaminoacids are formed, even in proteins that do not appear to have mechanisms for inserting selenocysteine by cotranslational processes; these selenoaminoacids typically show divergence in their chromatographic properties from the known selenoaminoacids, and tend to be found with the more hydrophobic residues. It is the purpose of this study to clarify the nature of the selenoaminoacids or related forms found in proteins of animals following in vivo or in vitro labeling with radioactive inorganic selenium. The hypothesis to be tested is that selenium is metabolized to reactive intermediates that bind covalently to protein targets. These proteins may selectively labeled because of their proximity to the site where the reactive intermediates are generated, as well as having certain types of aminoacid residues (hydrophobic) that are more likely to undergo reactions with the reactive selenium intermediates. It is emphasized that in long-term dietary supplementation of humans with selenium, these modification reactions may be significant in regard to certain biological effects of selenium such as anticarcinogenic action, as well as undesirable toxic side effects.